Abstract
It has been established that hydrogen peroxide (H2O2) acts as a signalling messenger by triggering the reversible oxidation of redox-regulated proteins via a redox-relay provided by peroxiredoxins (Prdxs). Exceptionally high reactivity of Prdxs with H2O2 exceeding other thiols by orders of magnitude places Prdxs as sensors of H2O2 and distributers of oxidizing equivalents to specific thiol targets which can't be oxidized by H2O2 directly. By this mechanism the oxidative stress response can be achieved.
Despite its involvement in oxidative stress responses, H2O2 is continuously generated as a normal metabolite necessary for regular cell functioning. The challenge lies in understanding how the Prdx-dependent redox relay can differentiate between basal levels of H2O2 and excessive amounts that lead to oxidative stress.
Peroxymonocarbonate, an oxidant formed when H2O2 reacts with CO2/HCO3−, emerges as a potent cellular oxidant. The peroxymonocarbonate formation could be catalysed and then consumed at localised sites by certain thiol proteins. This mechanism could prevent H2O2 from reacting with Prdx, thereby averting the redox-relayed activation of regulatory thiol proteins and subsequent oxidative stress response below a certain level of H2O2.